In January 2008, CDP and the Office of Rare Diseases sponsored a workshop that focused on facilitating the use of cancer stem cells (CSC) as markers of outcome and response to therapy. It brought together 30 investigators to review the current status of CSC in clinical trials, to define the barriers for evaluating the CSC hypothesis, and then to consider how to move the field forward. Since this workshop focused on CSC as markers of prognosis and/or therapeutic response, it addressed the assays and technologies to reliably detect CSC and study designs for assessing clinical utility rather than on the biology and specific treatment of CSC. The workshop focused on breast cancer, the leukemias, and multiple myeloma in depth as paradigms for testing the stem cell hypothesis with experiences gleaned from other human malignancies. The workshop also analyzed in depth whether optical imaging technologies are sufficiently reliable to support measurement of CSC in clinical samples. The workshop resulted in two Small Business Innovation Research contract solicitations that have funded tissue-based optical imaging advances.